期刊
ARTHRITIS RESEARCH & THERAPY
卷 14, 期 2, 页码 -出版社
BIOMED CENTRAL LTD
DOI: 10.1186/ar3812
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类别
资金
- UCB
- Office of Research and Development
- Medical Research Service
- Department of Veterans Affairs
- Frederick G. L. Huetwell and William D. Robinson MD Professorship in Rheumatology
Introduction: TNF alpha is a proinflammatory cytokine that plays a central role in the pathogenesis of rheumatoid arthritis (RA). We investigated the effects of certolizumab pegol, a TNF alpha blocker, on endothelial cell function and angiogenesis. Methods: Human dermal microvascular endothelial cells (HMVECs) were stimulated with TNF alpha with or without certolizumab pegol. TNF alpha-induced adhesion molecule expression and angiogenic chemokine secretion were measured by cell surface ELISA and angiogenic chemokine ELISA, respectively. We also examined the effect of certolizumab pegol on TNF alpha-induced myeloid human promyelocytic leukemia (HL-60) cell adhesion to HMVECs, as well as blood vessels in RA synovial tissue using the Stamper-Woodruff assay. Lastly, we performed HMVEC chemotaxis, and tube formation. Results: Certolizumab pegol significantly blocked TNF alpha-induced HMVEC cell surface angiogenic E-selectin, vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 expression and angiogenic chemokine secretion (P < 0.05). We found that certolizumab pegol significantly inhibited TNF alpha-induced HL-60 cell adhesion to HMVECs (P < 0.05), and blocked HL-60 cell adhesion to RA synovial tissue vasculature (P < 0.05). TNF alpha also enhanced HMVEC chemotaxis compared with the negative control group (P < 0.05) and this chemotactic response was significantly reduced by certolizumab pegol (P < 0.05). Certolizumab pegol inhibited TNF alpha-induced HMVEC tube formation on Matrigel (P < 0.05). Conclusion: Our data support the hypothesis that certolizumab pegol inhibits TNF alpha-dependent leukocyte adhesion and angiogenesis, probably via inhibition of angiogenic adhesion molecule expression and angiogenic chemokine secretion.
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